"The advantage that is seen with chemotherapy alone is due to the fact that there are fewer deaths from causes other than progressive Hodgkin's lymphoma or acute treatment-related toxic effects," say Ralph Meyer (Queens University, Kingston, Ontario, Canada) and co-authors of the study.

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The researchers explain that chemotherapy plus radiation treatment effectively controls stage IA or IIA nonbulky Hodgkin's lymphoma in 90% of patients but is associated with late treatment-related deaths.

A total of 405 patients with previously untreated stage IA or IIA nonbulky Hodgkin's lymphoma were randomly assigned to treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy (four to six cycles) alone (n=196) or to treatment with subtotal nodal radiation therapy, with or without ABVD therapy (n=203 overall).

After a median follow-up period of 4.2 years, the researchers reported that the progression-free survival (PFS) rate was higher among patients assigned to radiation therapy than among those assigned to ABVD therapy alone, but no difference in overall survival was detected.

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In the current report, published in TheNew England Journal of Medicine, Meyer and team provide the final data analysis from this trial, conducted at the end of a median follow-up period of 11.3 years.

They observed a significant difference between the groups in the primary study endpoint of 12-year overall survival, at 94% among those receiving ABVD alone compared with 87% among those receiving subtotal nodal radiation therapy with or without ABVD. In absolute terms, there were 12 deaths in the ABVD group and 24 in the radiation-therapy group, which corresponds to a significant 50% relative reduction in the risk for death among patients receiving ABVD alone.

The researchers note that in the radiation-therapy group compared with the ABVD-only group there were more deaths due to second cancers (10 vs 4) and more deaths from causes other than Hodgkin's lymphoma or second cancers (10 vs 2).

In contrast to overall survival, patients in the ABVD group were significantly less likely than those in the radiation-therapy group to remain disease-free during follow up, at respective PFS rates of 87% and 92%. The risk for disease progression was 1.91-fold higher with ABVD than with radiation therapy.

Discussing their findings, Meyer and team accept that the subtotal radiation therapy they used is outdated, "and the extent of radiation therapy is very likely to have contributed to the excess deaths."

Furthermore, the study overlapped with two "practice-changing" international trials (H8F and HD10), which showed "excellent" outcomes with combination therapy that included involved-field radiation therapy. The overall survival rates in these trials were 97% at 10 years and 95% at 8 years, respectively.

However, the shorter follow-up period of these two trials indicates that they "are not definitely superior" to those observed with ABVD alone in HD.6, Meyer et al remark.

They therefore conclude: "Treatment with ABVD therapy alone is a legitimate choice for patients with stage IA or IIA nonbulky Hodgkin's lymphoma."